Pupillometric Assessment of Small Doses of Opioid in a Pediatric Population

According to the CDC, opioid prescriptions in the United States have more than tripled from 1999-2014, which has correlated with the staggering increase in opioid-involved drug overdose deaths. This pattern of prescription is thought to be a major contributory factor to the increase in drug overdose in America, as four out of five new heroin users started by misusing prescription painkillers. Providers need the means to objectively monitor analgesic efficacy of treatment in patients with pain to mitigate unnecessary analgesic prescribing. It is well established that mu opioid agonists like morphine cause miosis, an effect to which tolerance does not occur. This suggests a utility in using pupil size and responsiveness as a pharmacokinetic analogue of bioavailability. An infrared pupillometer is a device that produces a short light stimulus and subsequently measures parameters of the pupillary light reflex (PLR) including maximum and minimum pupil size (MAX, MIN), maximum constriction velocity (MCV), latency period before constriction onset (LAT), change in pupil size (DELTA), and average constriction velocity (ACV). Current data supports the efficacy of using infrared pupillometry to detect high dose opioid presence, but no research exists judging its efficacy in monitoring low dose therapeutic levels. We enrolled 15 patients between the ages of 7 and 18 on the pain medicine service receiving low dose opioids on patient controlled analgesia (PCA). The pupillometer was used to take a baseline PLR, and repeated measures were taken 10 and 15-minutes post PCA dose infusion. We found that the pupil size at 10 and 15-minute time points were significantly smaller than the baseline for the parameters MAX (p=.0016, p=.0010) and MIN (p=.0250, p=.0070). Additionally, it was found that LAT was significantly longer from baseline at the 15-minute measure (p=.0350), and there was a significant difference between the 10 and 15-minute time points for the MIN (p=0.0251). This evidence supports the sensitivity of the pupillometer in evaluating opioid activity. Furthermore, in concordance with previous research, the MIN is significantly correlated with opioid concentration dose-dependently across the 15-minute measurement window. Before applying the pupillometer to clinical pain medicine, more research comparing pupillometric parameters with blood levels of opioid metabolites will serve to determine detection limits. Providers could use this tool to monitor treatment efficacy by using these parameters to assess steady state equilibrium and to determine dosing intervals. Furthermore, the pupillometric parameters could elucidate individuals’ metabolic capacity for different opioids in order to prescribe therapeutic levels

Subanesthetic ketamine infusions for the treatment of children and adolescents with chronic pain: a longitudinal study

Background Chronic pain is common in children and adolescents and is often associated with severe functional disability and mood disorders. The pharmacological treatment of chronic pain in children and adolescents can be challenging, ineffective, and is mostly based on expert opinions and consensus. Ketamine, an N-methyl-D-aspartate receptor antagonist, has been used as an adjuvant for treatment of adult chronic pain and has been shown, in some instances, to improve pain and decrease opioid-requirement. We examined the effects of subanesthetic ketamine infusions on pain intensity and opioid use in children and adolescents with chronic pain syndromes treated in an outpatient setting. Methods Longitudinal cohort study of consecutive pediatric patients treated with subanesthetic ketamine infusions in a tertiary outpatient center. Outcome measurements included self-reported pain scores (numeric rating scale) and morphine-equivalent intake. Results Over a 15-month period, 63 children and adolescents (median age 15, interquartile range 12–17 years) with chronic pain received 277 ketamine infusions. Intravenous administration of subanesthetic doses of ketamine to children and adolescents on an outpatient basis was safe and not associated with psychotropic effects or hemodynamic perturbations. Overall, ketamine significantly reduced pain intensity (p \u3c0.001) and yielded greater pain reduction in patients with complex regional pain syndrome (CRPS) than in patients with other chronic pain syndromes (p = 0.029). Ketamine-associated reductions in pain scores were the largest in postural orthostatic tachycardia syndrome (POTS) and trauma patients and the smallest in patients with chronic headache (p = 0.007). In 37 % of infusions, patients had a greater than 20 % reduction in pain score. Conversely, ketamine infusions did not change overall morphine-equivalent intake (p = 0.3). Conclusions These data suggest that subanesthetic ketamine infusion is feasible in an outpatient setting and may benefit children and adolescents with chronic pain. Further, patients with CRPS, POTS, and

Low-dose ketamine for children and adolescents with acute sickle cell disease related pain: A single center experience

Background: Opioids are the mainstay of therapy for painful vasoocclusive episodes (VOEs) in sickle cell disease (SCD). Based on limited studies, low-dose ketamine could be a useful adjuvant analgesic for refractory SCD pain, but its safety and efficacy has not been evaluated in pediatric SCD. Procedure: Using retrospective chart review we recorded and compared characteristics of hospitalizations of 33 children with SCD hospitalized with VOE who were treated with low-dose ketamine and opioid PCA vs. a paired hospitalization where the same patients received opioid PCA without ketamine. We seek to 1) describe a single center experience using adjuvant low-dose ketamine with opioid PCA for sickle cell related pain, 2) retrospectively explore the safety and efficacy of adjuvant low-dose ketamine for pain management, and 3) determine ketamine’s effect on opioid consumption in children and adolescents hospitalized with VOE. Results: During hospitalizations where patients received ketamine, pain scores and opioid use were higher (6.48 vs. 5.99; p=0.002 and 0.040 mg/kg/h vs. 0.032 mg/kg/h; p=0.004 respectively) compared to hospitalizations without ketamine. In 3 patients, ketamine was discontinued due to temporary and reversible psychotomimetic effects. There were no additional short term side effects of ketamine. Conclusions: Low-dose ketamine has an acceptable short-term safety profile for patients with SCD hospitalized for VOE. Lack of an opioid sparing effect of ketamine likely represents use of low-dose ketamine for patients presenting with more severe VOE pain. Prospective randomized studies of adjuvant low-dose ketamine for SCD pain are warranted to determine efficacy and long-term safety

Microbial rhodopsins on leaf surfaces of terrestrial plants

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Environmental Microbiology 14 (2012): 140-146, doi:10.1111/j.1462-2920.2011.02554.x.The above-ground surfaces of terrestrial plants, the phyllosphere, comprise the main interface between the terrestrial biosphere and solar radiation. It is estimated to host up to 1026 microbial cells that may intercept part of the photon flux impinging on the leaves. Based on 454- pyrosequencing generated metagenome data, we report on the existence of diverse microbial rhodopsins in five distinct phyllospheres from tamarisk (Tamarix nilotica), soybean (Glycine max), Arabidopsis (Arabidopsis thaliana), clover (Trifolium repens) and rice (Oryza sativa). Our findings, for the first time describing microbial rhodopsins from non-aquatic habitats, point toward the potential coexistence of microbial rhodopsin-based phototrophy and plant chlorophyll-based photosynthesis, with the different pigments absorbing non-overlapping fractions of the light spectrum.This work was supported in part by a grant from Bridging the Rift Foundation (O.B. & S.B.), Israel Science Foundation grant 1203/06 (O.B.), the Gruss-Lipper Family Foundation at MBL (O.M.F., S.B. & A.F.P.), a US-Israel Binational Science Foundation grant 2006324 (S.B.), and DOE National Institutes of Health Grant R37GM27750, Department of Energy Grant DE-FG02-07ER15867, and endowed chair AU-0009 from the Robert A. Welch Foundation (J.L.S.)

Effects of rising temperature on pelagic biogeochemistry in mesocosm systems: a comparative analysis of the AQUASHIFT Kiel experiments

A comparative analysis of data, obtained during four indoor-mesocosm experiments with natural spring plankton communities from the Baltic Sea, was conducted to investigate whether biogeochemical cycling is affected by an increase in water temperature of up to 6 °C above present-day conditions. In all experiments, warming stimulated in particular heterotrophic bacterial processes and had an accelerating effect on the temporal development of phytoplankton blooms. This was also mirrored in the build-up and partitioning of organic matter between particulate and dissolved phases. Thus, warming increased both the magnitude and rate of dissolved organic carbon (DOC) build-up, whereas the accumulation of particulate organic carbon (POC) and phosphorus (POP) decreased with rising temperature. In concert, the observed temperature-mediated changes in biogeochemical components suggest strong shifts in the functioning of marine pelagic food webs and the ocean’s biological carbon pump, hence providing potential feedback mechanisms to Earth’s climate system

A Multisite Preregistered Paradigmatic Test of the Ego-Depletion Effect

We conducted a preregistered multilaboratory project (k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result (d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect (d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.</p

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

Peer reviewe